Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2VJ767)

• DOT Name: CYFIP-related Rac1 interactor A (CYRIA)
• Synonyms: Protein CYRIA
• Gene Name: CYRIA
• Related Disease: Isolated cleft lip
• UniProt ID: CYRIA_HUMAN
• Pfam ID: PF07159
• Sequence:
  MGNLLKVLTREIENYPHFFLDFENAQPTEGEREIWNQISAVLQDSESILADLQAYKGAGP
  EIRDAIQNPNDIQLQEKAWNAVCPLVVRLKRFYEFSIRLEKALQSLLESLTCPPYTPTQH
  LEREQALAKEFAEILHFTLRFDELKMRNPAIQNDFSYYRRTISRNRINNMHLDIENEVNN
  EMANRMSLFYAEATPMLKTLSNATMHFVSENKTLPIENTTDCLSTMTSVCKVMLETPEYR
  SRFTSEETLMFCMRVMVGVIILYDHVHPVGAFCKTSKIDMKGCIKVLKEQAPDSVEGLLN
  ALRFTTKHLNDESTSKQIRAMLQ
• Function: May negatively regulate RAC1 signaling and RAC1-driven cytoskeletal remodeling (Probable). May regulate chemotaxis, cell migration and epithelial polarization by controlling the polarity, plasticity, duration and extent of protrusions (Probable).

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Isolated cleft lip	DIS2O2JV	Strong	Genetic Variation	[1]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of CYFIP-related Rac1 interactor A (CYRIA).	[2]

11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of CYFIP-related Rac1 interactor A (CYRIA).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of CYFIP-related Rac1 interactor A (CYRIA).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of CYFIP-related Rac1 interactor A (CYRIA).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of CYFIP-related Rac1 interactor A (CYRIA).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of CYFIP-related Rac1 interactor A (CYRIA).	[7]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of CYFIP-related Rac1 interactor A (CYRIA).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of CYFIP-related Rac1 interactor A (CYRIA).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of CYFIP-related Rac1 interactor A (CYRIA).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of CYFIP-related Rac1 interactor A (CYRIA).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of CYFIP-related Rac1 interactor A (CYRIA).	[11]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of CYFIP-related Rac1 interactor A (CYRIA).	[12]

References

• [1] Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity.Nat Commun. 2017 Feb 24;8:14364. doi: 10.1038/ncomms14364.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [9] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [10] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [11] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [12] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.